Current advances in biopharmaceutical informatics: guidelines, impact and challenges in the computational developability assessment of antibody therapeutics.

Autor: Khetan R; Manchester Institute of Biotechnology, University of Manchester, Manchester, UK., Curtis R; Manchester Institute of Biotechnology, University of Manchester, Manchester, UK., Deane CM; Department of Statistics, University of Oxford, Oxford, UK., Hadsund JT; Department of Mathematics and Computer Science, University of Southern Denmark, Odense, Denmark., Kar U; Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA, USA., Krawczyk K; NaturalAntibody, Hamburg, Germany., Kuroda D; Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, Japan.; Medical Device Development and Regulation Research Center, School of Engineering, The University of Tokyo, Tokyo, Japan.; Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo, Japan., Robinson SA; Department of Statistics, University of Oxford, Oxford, UK., Sormanni P; Chemistry of Health, Yusuf Hamied Department of Chemistry, University of Cambridge., Tsumoto K; Department of Bioengineering, School of Engineering, The University of Tokyo, Tokyo, Japan.; Medical Device Development and Regulation Research Center, School of Engineering, The University of Tokyo, Tokyo, Japan.; Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo, Japan.; The Institute of Medical Science, The University of Tokyo, Tokyo, Japan., Warwicker J; Manchester Institute of Biotechnology, University of Manchester, Manchester, UK., Martin ACR; Institute of Structural and Molecular Biology, Division of Biosciences, University College London, London, UK.
Jazyk: angličtina
Zdroj: MAbs [MAbs] 2022 Jan-Dec; Vol. 14 (1), pp. 2020082.
DOI: 10.1080/19420862.2021.2020082
Abstrakt: Therapeutic monoclonal antibodies and their derivatives are key components of clinical pipelines in the global biopharmaceutical industry. The availability of large datasets of antibody sequences, structures, and biophysical properties is increasingly enabling the development of predictive models and computational tools for the "developability assessment" of antibody drug candidates. Here, we provide an overview of the antibody informatics tools applicable to the prediction of developability issues such as stability, aggregation, immunogenicity, and chemical degradation. We further evaluate the opportunities and challenges of using biopharmaceutical informatics for drug discovery and optimization. Finally, we discuss the potential of developability guidelines based on in silico metrics that can be used for the assessment of antibody stability and manufacturability.
Databáze: MEDLINE